Alpha, alpha diaryl piperidino methanols



uum distilled on the steam bath. The residue was Patented Jan. 6, 1953 UNITED STATES ZRATBNT "OFFICE ALEHAALPHA DIARYL PIPERIDINO METHANOLS Harold W. Vierner, Sharonviile, and Charles H. Tilford, Silverton, Ohio, assignors to The Wm. S. Merrell Company, Cincinnati, Ohio, a corporation of Delaware No Drawing. Application November 23, 1949, Serial No. 129,182

3 Claims. (Cl. 260-29437) This invention relates to new chemical comrecrystallized from butanone to give the desired pounds which are useful stimulants for the cenproduct which melted at 228-229 (dec.). tral nervous system. Example III. AZpha-phenyl-aZpha-methyZ-Z- These compounds are derivatives of a1pha-(2- piperz'dinemethanoL-A solution of 30 grams piperidyl) -benzyl alcohol or certain homologues 5 (0.13 mole) of alpha phenyl alpha methyl-2- thereof and are comprehended by the generic forpyridinemethanol hydrochloride in 100 ml. of ethmula anol was shaken at '70-80 at an initial hydrogen pressure of 50 pounds in the presence of 0.4 gram R of Adams platinum catalyst. The theoretical amount of hydrogen was absorbed in one hour. s R3 The mixture was filtered and the filtrate was 0-122 evaporated on the steam bath. The residue was N 5 recrystallized from butan'one. The yield of white in crystalline hydrochloride was 24 grams (80%);

Example IV. Alpha-phenyZ-aZpha-methyZ-1- methyl-2-piperidinemethancl.A mixture of grams (0.1 mole) of the above 2-piperidinemethanol, 32 grams (0.65 mole) of 90% formic acid 20 and 16 grams (0.195 mole) of formalin was refluxed forty-eight hours. The reaction mixture atolyl radicaL was made alkaline with sodium hydroxide,

The new compounds may in general be extracted with benzene, and the benzene extract pared by reduction of the Corresponding pyridine fractionally distilled through a 20 cm. Vigreux compounds, the N-alkyl compounds bein ob 25 column. The product distilling at 125-129 (0.4 tained by the introduction of a methyl or ethyl mm) amounted to 20 grams (91%)- A Sample in which the nitrogen-containing ring is saturated as signified by S (that is, is a piperidine ring), R. and R1 are hydrogen atoms or the methyl or ethyl radicals and are alike or different, R2 is the methyl, ethyl or phenyl radical or a tolyl 0r methoxyphenyl radical, and R3 is the phenyl or radical into the corresponding compound in hi h was converted to the white crystalline hydrochlo- R1 of the generic formula is hydrogen. These nae; -2

features are illustrated by the followin specific modificatlon 0f the p c dures of the speexamples, which are not 1imitative 3o cific examples in known manner, the other com- Ezcample I .AZp7m,aZpha-diphenyl 2 piperipounds of this invention can be prepared.

dinemethan-0Z.A mixture of 48 grams (0.167 The ew compounds are basic, and will ordimole) of alpha,alpha-diphenyl-2-pyridi t narily be used in the form of an acid addition salt,

anol hydrochloride (Emmert et al., Ber. 72B, 1188 the hydrochloride, mido, Sulfate, (1939); 74B, 714 (1949), 160 m1. of ethanol, and 5 n e, phosph lv acetate, tartrato. 0.5 gram of Adams platinum catalyst was shaken lei/1111115136, the like, y oral administration in under an hydrogen pressure of 69 pounds the form Of tablets 01' other suitable form. The The theoretical amount of hydrogen was abnew compounds y also e administered p r sorbed in 5 hours. The reaction mixture was reterally, o e amp t o yfluxed, diluted with enough water to dissolve all We Claim! the white solid, and filtered hot from the catalyst. l. The compounds of the generic formula The filtrate was cooled and filtered; yield: 38 grams of white product melting at 308-309 with R decomposition. S

Anal. calcd. for C18H21ON.HC1Z 01, 11.75. N Found: Cl, 11.85. 5

Example II .--Alpha, aZpha-diphenyZ-l-methyl- R1 Z-piperz'dinemethanol hydrochZoricZe.-A mixture in which 6 signifies that the nitrogen-containing of 3.5 grams (0.013 mole) of the above alpha,- ring is saturated, R115 a substituent selected from alpha-diphenyl 2 piperidinemethanol, 4 grams the group consisting of the hydrogen atom and (0.05 mole) of formaldehyde (37%), and 6 grams methyl and ethyl radicals, R2 is a substituent (0.1 mole) of formic acid was refluxed for 2 days. selected from the group consistin of the phenyl, The reaction mixture was treated with 1.3 grams tolyl and methoxyphenyl radicals, and R3 is a sub- (0.013 mole) of cone. hydrochloric acid and vacstituent selected from the group consisting of the phenyl and tolyl radicals.

3 '4 2. Alpha,alpha diphenyl Z-piperidinemeth- Anker et 91.: Chem. Abs., vol. 40 (1946),p. 1836. anol. Renshaw et aL: Chem. Abs., v01. 33 (1939), p.

3. A1pha,a1pha diphenyl l-methyl-Z-piperi- 3379.

dinemethanol. Winterfeld et al.: Chem. Abs., v01. 29 (1935), p.

HAROLD W. WERNER. 5 7331.

CHARLES H. TILFORD. Emmert et a1.: Ber. Deut. Chem., vol. 723, pp.

REFERENCES CITED Tilford et aL: J. Am. Chem. Soc., vol. 70, pp.

The following references are of record in the 4001-4009 (1948)- file of this patent: 10 

1. THE COMPOUNDS OF THE GENERAL FORMULA 